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- Publisher Website: 10.1016/j.bmcl.2011.03.063
- Scopus: eid_2-s2.0-79955561585
- PMID: 21481589
- WOS: WOS:000290024200033
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Article: New aromatic substituted pyrazoles as selective inhibitors of human adipocyte fatty acid-binding protein
Title | New aromatic substituted pyrazoles as selective inhibitors of human adipocyte fatty acid-binding protein | ||||||||
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Authors | |||||||||
Keywords | a-FABP inhibitor Aromatic substituted pyrazoles Inflammation related diseases Inflammatory response | ||||||||
Issue Date | 2011 | ||||||||
Publisher | Pergamon. The Journal's web site is located at http://www.elsevier.com/locate/bmcl | ||||||||
Citation | Bioorganic And Medicinal Chemistry Letters, 2011, v. 21 n. 10, p. 2949-2952 How to Cite? | ||||||||
Abstract | a-FABP is indespensible in inflammation and may serve as a new potential drug target for inflammation related diseases. We have successfully designed and synthesized a series of aromatic substituted pyrazoles as new human a-FABP inhibitors. The compounds strongly bound to the hydrophobic binding pocket of a-FABP, while showed significantly lower binding affinities to the closely related homologue protein h-FABP. The most potent and selective compound 5g bound to a-FABP with an apparent K i value below 1.0 nM, while did not inhibit h-FABP at 50 μM and thus represents one of the most potent and selective a-FABP inhibitors to date. The strong binding capacity of these inhibitors was further validated by their effective blockade of inflammatory responses as determined by the production of pro-inflammatory cytokines upon LPS stimulation. Compound 5g may serve as a lead compound for developing new effective therapeutic agent for prevention and treatment of atherosclerosis, type 2 diabetes and other inflammatory and metabolic related diseases. © 2011 Elsevier Ltd. All rights reserved. | ||||||||
Persistent Identifier | http://hdl.handle.net/10722/139452 | ||||||||
ISSN | 2023 Impact Factor: 2.5 2023 SCImago Journal Rankings: 0.508 | ||||||||
ISI Accession Number ID |
Funding Information: We thank National Basic Research Program of China (Grant #2010CB529706, 2010CB9455000 and 2009CB940904), the 100-talent program of Chinese Academy of Sciences, and National Natural Science Foundation (Grant #30811120429, 3097063 and 90813033) for their financial support. | ||||||||
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Liu, X | en_HK |
dc.contributor.author | Huang, X | en_HK |
dc.contributor.author | Lin, W | en_HK |
dc.contributor.author | Wang, D | en_HK |
dc.contributor.author | Diao, Y | en_HK |
dc.contributor.author | Li, H | en_HK |
dc.contributor.author | Hui, X | en_HK |
dc.contributor.author | Wang, Y | en_HK |
dc.contributor.author | Xu, A | en_HK |
dc.contributor.author | Wu, D | en_HK |
dc.contributor.author | Ke, D | en_HK |
dc.date.accessioned | 2011-09-23T05:50:09Z | - |
dc.date.available | 2011-09-23T05:50:09Z | - |
dc.date.issued | 2011 | en_HK |
dc.identifier.citation | Bioorganic And Medicinal Chemistry Letters, 2011, v. 21 n. 10, p. 2949-2952 | en_HK |
dc.identifier.issn | 0960-894X | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/139452 | - |
dc.description.abstract | a-FABP is indespensible in inflammation and may serve as a new potential drug target for inflammation related diseases. We have successfully designed and synthesized a series of aromatic substituted pyrazoles as new human a-FABP inhibitors. The compounds strongly bound to the hydrophobic binding pocket of a-FABP, while showed significantly lower binding affinities to the closely related homologue protein h-FABP. The most potent and selective compound 5g bound to a-FABP with an apparent K i value below 1.0 nM, while did not inhibit h-FABP at 50 μM and thus represents one of the most potent and selective a-FABP inhibitors to date. The strong binding capacity of these inhibitors was further validated by their effective blockade of inflammatory responses as determined by the production of pro-inflammatory cytokines upon LPS stimulation. Compound 5g may serve as a lead compound for developing new effective therapeutic agent for prevention and treatment of atherosclerosis, type 2 diabetes and other inflammatory and metabolic related diseases. © 2011 Elsevier Ltd. All rights reserved. | en_HK |
dc.language | eng | en_US |
dc.publisher | Pergamon. The Journal's web site is located at http://www.elsevier.com/locate/bmcl | en_HK |
dc.relation.ispartof | Bioorganic and Medicinal Chemistry Letters | en_HK |
dc.subject | a-FABP inhibitor | en_HK |
dc.subject | Aromatic substituted pyrazoles | en_HK |
dc.subject | Inflammation related diseases | en_HK |
dc.subject | Inflammatory response | en_HK |
dc.subject.mesh | Adipocytes - drug effects | - |
dc.subject.mesh | Anti-Inflammatory Agents - chemical synthesis - chemistry - pharmacology | - |
dc.subject.mesh | Drug Design | - |
dc.subject.mesh | Fatty Acid-Binding Proteins - antagonists and inhibitors | - |
dc.subject.mesh | Pyrazoles - chemical synthesis - chemistry - pharmacology | - |
dc.title | New aromatic substituted pyrazoles as selective inhibitors of human adipocyte fatty acid-binding protein | en_HK |
dc.type | Article | en_HK |
dc.identifier.email | Wang, Y: yuwanghk@hku.hk | en_HK |
dc.identifier.email | Xu, A: amxu@hkucc.hku.hk | en_HK |
dc.identifier.authority | Wang, Y=rp00239 | en_HK |
dc.identifier.authority | Xu, A=rp00485 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.bmcl.2011.03.063 | en_HK |
dc.identifier.pmid | 21481589 | - |
dc.identifier.scopus | eid_2-s2.0-79955561585 | en_HK |
dc.identifier.hkuros | 194038 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-79955561585&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 21 | en_HK |
dc.identifier.issue | 10 | en_HK |
dc.identifier.spage | 2949 | en_HK |
dc.identifier.epage | 2952 | en_HK |
dc.identifier.eissn | 1464-3405 | - |
dc.identifier.isi | WOS:000290024200033 | - |
dc.publisher.place | United Kingdom | en_HK |
dc.identifier.scopusauthorid | Liu, X=49861829500 | en_HK |
dc.identifier.scopusauthorid | Huang, X=9940392000 | en_HK |
dc.identifier.scopusauthorid | Lin, W=36717896600 | en_HK |
dc.identifier.scopusauthorid | Wang, D=14051219700 | en_HK |
dc.identifier.scopusauthorid | Diao, Y=36617062800 | en_HK |
dc.identifier.scopusauthorid | Li, H=36064230500 | en_HK |
dc.identifier.scopusauthorid | Hui, X=26666795900 | en_HK |
dc.identifier.scopusauthorid | Wang, Y=34973733700 | en_HK |
dc.identifier.scopusauthorid | Xu, A=7202655409 | en_HK |
dc.identifier.scopusauthorid | Wu, D=7404297751 | en_HK |
dc.identifier.scopusauthorid | Ke, D=35332543000 | en_HK |
dc.identifier.issnl | 0960-894X | - |